Behavior Genetics

, Volume 43, Issue 2, pp 132–140 | Cite as

Xq27 FRAXA Locus is a Strong Candidate for Dyslexia: Evidence from a Genome-Wide Scan in French Families

  • M. Huc-Chabrolle
  • C. Charon
  • A. Guilmatre
  • P. Vourc’h
  • G. Tripi
  • M. A. Barthez
  • E. Sizaret
  • R. A. Thepault
  • S. Le Gallic
  • J. Hager
  • A. Toutain
  • M. Raynaud
  • C. Andres
  • D. Campion
  • F. Laumonnier
  • F. Bonnet-Brilhault
Original Research

Abstract

Dyslexia is a frequent neurodevelopmental learning disorder. To date, nine susceptibility loci have been identified, one of them being DYX9, located in Xq27. We performed the first French SNP linkage study followed by candidate gene investigation in dyslexia by studying 12 multiplex families (58 subjects) with at least two children affected, according to categorical restrictive criteria for phenotype definition. Significant results emerged on Xq27.3 within DYX9. The maximum multipoint LOD score reached 3,884 between rs12558359 and rs454992. Within this region, seven candidate genes were investigated for mutations in exonic sequences (CXORF1, CXORF51, SLITRK2, FMR1, FMR2, ASFMR1, FMR1NB), all having a role during brain development. We further looked for 5′UTR trinucleotide repeats in FMR1 and FMR2 genes. No mutation or polymorphism co-segregating with dyslexia was found. This finding in French families with Dyslexia showed significant linkage on Xq27.3 enclosing FRAXA, and consequently confirmed the DYX9 region as a robust susceptibility locus. We reduced the previously described interval from 6.8 (DXS1227–DXS8091) to 4 Mb also disclosing a higher LOD score.

Keywords

Dyslexia Linkage study Multiplex families Fmr1 Dyx 9 loci 

Supplementary material

10519_2012_9575_MOESM1_ESM.ppt (191 kb)
Supplementary Table 1 (PPT 191 kb)
10519_2012_9575_MOESM2_ESM.ppt (404 kb)
Supplementary Table 2 (PPT 404 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • M. Huc-Chabrolle
    • 1
    • 2
    • 7
    • 9
  • C. Charon
    • 3
  • A. Guilmatre
    • 4
  • P. Vourc’h
    • 1
    • 5
  • G. Tripi
    • 2
    • 6
  • M. A. Barthez
    • 7
  • E. Sizaret
    • 7
  • R. A. Thepault
    • 1
    • 5
  • S. Le Gallic
    • 4
  • J. Hager
    • 3
  • A. Toutain
    • 1
    • 8
  • M. Raynaud
    • 1
    • 8
  • C. Andres
    • 1
    • 5
  • D. Campion
    • 4
  • F. Laumonnier
    • 1
    • 8
  • F. Bonnet-Brilhault
    • 1
    • 2
    • 7
  1. 1.UMR INSERM U930François Rabelais UniversityToursFrance
  2. 2.Department of Child PsychiatryUniversity Hospitals of ToursToursFrance
  3. 3.CEA/Centre National de GénotypageÉvryFrance
  4. 4.INSERM U 1079RouenFrance
  5. 5.Department of Molecular BiochemistryUniversity Hospitals of ToursToursFrance
  6. 6.University of PalermoPalermoItaly
  7. 7.Reference Centre for Learning DisabilityUniversity Hospitals of ToursToursFrance
  8. 8.Department of Human GeneticsUniversity Hospitals of ToursToursFrance
  9. 9.Centre Universitaire de Pédopsychiatrie, CHRU de Tours, Hôpital BretonneauTours Cedex 9France

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